Evaluation of Dabigatran Bleeding Adverse Reaction Reports in the FDA Adverse Event Reporting System during the First Year of Approval

Authors

  • Kevin W. McConeghy,

    Corresponding author
    1. Department of Pharmacy Practice University of Illinois at Chicago, Chicago, Illinois
    • Author for correspondence: Kevin McConeghy, Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60612; e-mail: kwm@uic.edu.

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  • Adam Bress,

    1. Department of Pharmacy Practice University of Illinois at Chicago, Chicago, Illinois
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  • Dima M. Qato,

    1. Department of Pharmacy Practice University of Illinois at Chicago, Chicago, Illinois
    2. Department of Pharmacy Systems, Outcomes and Policy, University of Illinois at Chicago, Chicago, Illinois
    3. Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, Illinois
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  • Coady Wing,

    1. Division of Health Policy and Administration, University of Illinois at Chicago, Chicago, Illinois
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  • Edith A. Nutescu

    1. Department of Pharmacy Practice University of Illinois at Chicago, Chicago, Illinois
    2. Department of Pharmacy Systems, Outcomes and Policy, University of Illinois at Chicago, Chicago, Illinois
    3. Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, Illinois
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  • Disclosures: Edith A. Nutescu is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K23HL112908. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Edith A. Nutescu also receives research support from Janssen Health Economics and Outcomes Research and The Cranberry Institute. She serves on the board of regents for the American College of Clinical Pharmacy, board of directors of the Anticoagulation Forum, and the Medical and Scientific Advisory Board for the National Blood Clot Alliance. She serves as consultant for Janssen Health Economics and Outcomes Research, Daichii Sankyo, and CSL Behring. There are no other relevant disclosures for any of the other authors.
  • Preliminary results of this study were presented at the American College of Cardiology 13th Annual Meeting, San Francisco, CA, March 9–11, 2013. J Am Coll Cardiol 2013;61:10S.

Abstract

Study Objective

Evaluate dabigatran adverse event reports with a reported bleeding event and/or reported fatal outcome compared with warfarin.

Design

Retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database.

Measurements and Main Results

We identified reports from October 1, 2010, through December 31, 2011, in the United States listing dabigatran or warfarin as the primary suspected agent. Bleeding events and related outcomes were determined. A bleeding-related mortality rate was calculated based on national dabigatran treatment data.

Results

Dabigatran was the primary suspected agent in 9029 adverse reports. Of these, 2347 (26%) were bleeding events; a fatal outcome was reported in 348 (15%) of the bleeding events. In comparison, warfarin was the suspected agent in 2038 reports, of which 647 (32%) were reported as bleeding events. Among the warfarin bleeding reports, 46 (7.1%) reported a fatal outcome. Based on national dabigatran use and adverse bleed reports with fatal outcomes, we estimate a lower bound of 150 bleeding-related fatalities per 100,000 dabigatran patient-years. Because of underreporting bias, these estimates represent a lower bound on the population bleeding mortality rates.

Conclusion

Reports from FAERS are subject to significant bias but suggest that fatal outcomes among dabigatran reports are higher in clinical practice than they were in controlled clinical trials.

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